Natural products are a major source of small molecular weight angiogenesis inhibitors, and the transformed endothelial cell line SVR has been used to screen natural product extracts to isolate anti-angiogenesis and anti-tumor compounds (Arbiser et al., J. Biol. Chem., Vol. 278, Issue 37, 35501-35507, Sep. 12, 2003).
Aqueous extracts of Magnolia grandiflora exhibit potent activity in these SVR proliferation assays, and the small molecular weight compound honokiol is the active principle of magnolia extract. Honokiol has the following formula:

Honokiol exhibits potent anti-proliferative activity against SVR cells in vitro. In addition, honokiol demonstrates preferential inhibition of primary human endothelial cells compared with fibroblasts, and this inhibition was antagonized by antibodies against TNFα-related apoptosis-inducing ligand. In vivo, honokiol is highly effective against angiosarcoma in nude mice. Preclinical data suggests that honokiol is a systemically available and non-toxic inhibitor of angiogenesis, and also promotes apoptosis.
There remains a need for treatment of cancer that does not have the adverse effects generally caused by non-selectivity, of conventional chemotherapeutic agents. While honokiol is an active compound, it would be advantageous to develop hexafluoro-honokiol analogs that are even more active. The present invention provides such analogs, as well as pharmaceutical compositions including the analogs, and methods of treating cancer using the analogs.